Upper airway collapsibility, loop gain and arousal threshold: an integrative therapeutic approach to obstructive sleep apnea

上气道塌陷、循环增益和唤醒阈值：阻塞性睡眠呼吸暂停的综合治疗方法

• 批准号: 10516957
• 负责人: ERIC JAMES KEZIRIAN
• 金额: $ 73.78万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2023-06-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10516957
• 关键词: Acetazolamide; Address; Air Movements; Algorithms; Anatomy; Apnea; Arousal; Breathing; Cardiovascular system; Cross-Over Studies; Dilator; Disease; Drowsiness; Effectiveness; Endoscopy; Eszopiclone; Evaluation; Failure; Functional disorder; Goals; Intervention; Investigation; Measurement; Measures; Morbidity - disease rate; Multiple Abnormalities; Muscle; Neurocognitive; Observational Study; Obstruction; Obstructive Sleep Apnea; Operative Surgical Procedures; Palate; Participant; Patients; Pattern; Pharmaceutical Preparations; Polysomnography; Postoperative Period; Procedures; Prospective cohort; Public Health; Quality of life; Randomized; Research; Resolution; Sedation procedure; Severities; Shapes; Sleep; Soft Palate; Source; Therapeutic; Tissues; Treatment Efficacy; airway obstruction; alternative treatment; base; efficacy evaluation; experience; improved; indexing; innovation; mortality; novel therapeutics; positive airway pressure; pressure; response; shape analysis; signal processing; success; surgery outcome; trait; ventilation

We propose to conduct a prospective cohort (observational) study of 150 participants with moderate to severe obstructive sleep apnea (OSA) unable to tolerate positive airway pressure who are undergoing drug-induced sleep endoscopy (DISE), including measurement of upper airway closing pressure (Pclose), and tissue-repositioning soft palate surgery. Before and 6 months after surgery, we will measure OSA severity (apnea-hypopnea index) with sleep studies (polysomnograms). Using our recently-validated polysomnography-based signal processing algorithm, we will systematically assess the underlying mechanisms of OSA (traits) and airflow shape (consistent with palate obstruction). The expected 90 participants without resolution of OSA after surgery (surgery failures) will participate in an experimental randomized crossover study of acetazolamide (1 month) and acetazolamide/eszopiclone combination (1 month). Polysomnograms will be performed with each treatment, with algorithm-based determination of traits. The research goals are: (1) to define how mechanistic traits modify effectiveness of anatomic treatment (surgery) and (2) to examine the therapeutic efficacy of surgery in combination with endotype-directed (especially loop gain- and arousal threshold-directed) treatment. Aim 1: To determine the mechanistic factors modifying the impact of soft palate surgery on airway collapsibility. Hypothesis: tissue-repositioning palate surgery will decrease airway collapsibility, with the decrease greater with palate-only obstruction (based on DISE and non-invasive airflow shape analysis). Aim 2: To evaluate the mechanistic factors modifying efficacy of soft palate surgery on OSA severity. Hypotheses: surgery efficacy will be independently associated with palate-only obstruction (DISE) and the following prior to surgery: lesser airway collapsibility, lesser loop gain, and greater arousal threshold. Aim 3: To evaluate the efficacy of combining surgery with loop gain and arousal threshold interventions. Hypotheses: In surgery failures (non-responders), lowering loop gain (acetazolamide) will lower OSA severity (expected response rate = 40%); efficacy will be associated with lesser postoperative (prior to medication) airway collapsibility and greater postoperative loop gain. Lowering loop gain and raising arousal threshold together (acetazolamide/eszopiclone) will further reduce OSA severity (expected response rate = 60%); efficacy will be associated with lesser postoperative airway collapsibility and the combination of greater postoperative loop gain and lesser postoperative arousal threshold.

我们建议对150名参与者进行一项前瞻性队列（观察）研究 中度至重度阻塞性睡眠呼吸暂停（OSA）无法忍受正气压 谁正在接受药物诱导的睡眠内窥镜检查（DISE），包括上层的测量 气道闭合压力（PCLOSE）和固定软pa骨手术。之前和6 手术后的几个月，我们将通过睡眠研究测量OSA严重程度（呼吸暂停指数） （多聚词）。使用我们最近验证的基于多聚会的信号处理 算法，我们将系统地评估OSA（特质）和气流的潜在机制 形状（与口感阻塞一致）。预期的90名参与者没有解决 手术后的OSA（手术失败）将参加实验的随机跨界 乙酰唑胺（1个月）和乙酰唑胺/埃索普酮组合（1个月）的研究。 每种处理都将进行多个多词，并确定基于算法的确定 特质。研究目标是：（1）定义机械特征如何修改的有效性 解剖治疗（手术）和（2）检查手术的治疗功效 与内型指导的结合（尤其是循环增益和唤醒阈值指导） 治疗。目的1：确定修改软的机械因素 气道可折叠性手术。假设：重新定位的pa酸手术将 减少气道可折叠性，随着刺激性阻塞的降低，降低较大（基于 疾病和非侵入性气流形状分析）。目标2：评估机械因素 修饰软pa手术对OSA严重程度的疗效。假设：手术功效将 与仅pa骨阻塞（DISE）独立相关 手术：较小的气道可折叠性，较小的循环增益和更大的唤醒阈值。目标3：到 评估将手术与循环增益和唤醒阈值相结合的功效 干预措施。假设：在手术失败（非反应器）中，降低了循环增益 （乙酰唑胺）将降低OSA的严重性（预期响应率= 40％）；功效将是 与术后较少（药物之前）气道可折叠性和更大的相关 术后循环增益。降低循环增益并同时提高唤醒阈值 （乙酰唑胺/埃索普林）将进一步降低OSA的严重性（预期响应率= 60％）； 功效将与术后气道可折叠性较低和组合有关 术后循环增益更大，术后唤醒阈值较小。